Approximately 30-50% of people undergoing allogeneic hematopoietic cell transplantation (HCT) will develop chronic graft-versus-host disease (GVHD), a syndrome characterized by multi-system inflammation and fibrosis that clinically resembles autoimmune diseases. Chronic GVHD is the leading cause of non-relapse mortality in two-year disease free survivors and a major cause of morbidity. In 2005, the NIH convened a consensus conference designed to improve clinical research methods in chronic GVHD. Recommendations from the conference have been published, and are called the """"""""NIH consensus criteria."""""""" During our previous funding period, we assembled a multi-center, longitudinal, observational study of 554 patients who were assessed every six months to test the NIH consensus criteria. We have published 6 papers (12 more submitted or in preparation) evaluating the consensus recommendations. Our results support the recommended definitions for chronic GVHD diagnosis and severity scoring. Specifically, we confirmed the poor prognosis associated with concurrent acute and chronic GVHD (overlap syndrome) and showed a higher non-relapse mortality and lower overall survival associated with moderate-severe chronic GVHD. However, our analyses did not support the recommended NIH measures to assess therapeutic response. In particular, calculated overall NIH response at 6 months correlated poorly with patient and provider-reported responses, and also did not predict subsequent non-relapse mortality and overall survival. Thus, if a new, promising treatment for chronic GVHD were available, the field does not have a validated measure that can serve as a primary endpoint in a clinical trial. To address this critical gap in the field, we propose developing two new tools, the chronic GVHD activity index (CGVHD-AI) and the chronic GVHD severity score (CGVHD-SS). The CGVHD-AI is intended for use as an overall measure of disease activity, so that change in the score from enrollment to follow-up reflects treatment effects. The CGVHD- SS is intended to serve as an intermediate endpoint that predicts eventual treatment success, even if that takes months to years to reach. Eleven centers will enroll 368 patients with chronic GVHD who are just starting initial or secondary therapy. Comprehensive assessments at enrollment and 6 months will collect the candidate patient-reported, provider-reported, and laboratory tests that will be considered for inclusion in the new measures. At 18 months after enrollment, patients will again be assessed with all measures. Using this information, we will develop and validate the CGVHD-AI and CGVHD-SS, thus allowing robust clinical trials in chronic GVHD.

Public Health Relevance

Chronic graft-versus-host disease (GVHD) is a serious complication that occurs when the bone marrow or stem cells from one person are transplanted into another person, usually for the treatment of a blood cancer or other blood disease. Chronic GVHD is the leading cause of death in people who are otherwise cured of their cancers, and it is a major predictor of poor quality of life and impaired ability to function. The goal of this study s to develop better methods to quickly and accurately determine if people are responding to treatment for chronic GVHD.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA118953-07
Application #
8616040
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Merritt, William D
Project Start
2005-12-01
Project End
2018-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
7
Fiscal Year
2014
Total Cost
$279,083
Indirect Cost
$77,563
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Deegan, Anthony J; Talebi-Liasi, Faezeh; Song, Shaozhen et al. (2018) Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions. Lasers Surg Med 50:183-193
Chronic GVHD Consortium (2018) Design and Patient Characteristics of the Chronic Graft-versus-Host Disease Response Measures Validation Study. Biol Blood Marrow Transplant 24:1727-1732
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Du, Jing; Flynn, Ryan; Paz, Katelyn et al. (2018) Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a novel biomarker in patients. Blood 131:1743-1754
Lee, Stephanie J; Nguyen, Tam D; Onstad, Lynn et al. (2018) Success of Immunosuppressive Treatments in Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 24:555-562
Lee, Stephanie J; Onstad, Lynn; Chow, Eric J et al. (2018) Patient-reported outcomes and health status associated with chronic graft-versus-host disease. Haematologica 103:1535-1541
Khera, Nandita; Hamilton, Betty K; Pidala, Joseph A et al. (2018) Employment, Insurance, and Financial Experiences of Patients with Chronic Graft-versus-Host Disease in North America. Biol Blood Marrow Transplant :
Martin, Paul J; Storer, Barry E; Inamoto, Yoshihiro et al. (2017) An endpoint associated with clinical benefit after initial treatment of chronic graft-versus-host disease. Blood 130:360-367
Lee, Stephanie J (2017) Classification systems for chronic graft-versus-host disease. Blood 129:30-37

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